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Leonurine affected homocysteine-methionine metabolism based on metabolomics and gut microbiota studies of clinical trial samples.
Liao, J, Suguro, R, Zhao, X, Yu, Y, Cui, Y, Zhu, YZ
Clinical and translational medicine. 2021;(10):e535
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Hyperhomocysteinaemia and the risk of recurrent venous thrombosis: results from the MEGA follow-up study.
Hensen, ADO, Lijfering, WM, Cannegieter, SC, Rosendaal, FR, van Hylckama Vlieg, A
British journal of haematology. 2019;(2):219-226
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Abstract
The measurement of homocysteine is still part of routine thrombosis or thrombophilia work-up in many thrombosis centres in the world. Previous observational studies have shown that hyperhomocysteinaemia is associated with an increased risk of first and recurrent venous thrombosis (VT). Randomised trials, however, showed no benefit of homocysteine-lowering therapy on the risk of first or recurrent VT. This discrepancy could be explained by incomplete adjustment for confounders in the observational studies. We investigated in a large population-based follow-up study whether if the levels of homocysteine and its metabolites, methionine and cysteine, were associated with recurrent VT. Approximately three months after discontinuation of anticoagulant treatment, homocysteine, methionine and cysteine concentrations were measured in 2210 patients with VT. During a median follow-up of 6·9 years, 340 patients developed a recurrence (incidence rate, 2·8/100 patient-years). We found that elevated homocysteine concentrations were not associated with an increased risk of recurrent VT, neither as a continuous variable per 5 μmol/l increase (hazard ratio [HR] 0·98 (95% confidence interval [CI], 0·90-1·04)) nor when levels were >95th (>23·0 μmol/l) percentile (HR 1·03 (95% CI, 0·65-1·64)). Similar results were obtained for cysteine and methionine values. We conclude that hyperhomocysteinaemia is not associated with an increased risk of recurrent VT.
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Double-blind placebo-controlled multicenter phase II trial to evaluate D-methionine in preventing/reducing oral mucositis induced by radiation and chemotherapy for head and neck cancer.
Hamstra, DA, Lee, KC, Eisbruch, A, Sunkara, P, Borgonha, S, Phillip, B, Campbell, KCM, Ross, BD, Rehemtulla, A
Head & neck. 2018;(7):1375-1388
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Abstract
BACKGROUND The purpose of this study was to test if oral D-methionine (D-met) reduced mucositis during chemoradiotherapy. METHODS We conducted a placebo-controlled double-blind randomized phase II trial of D-met (100 mg/kg p.o. b.i.d.) testing the rate of severe (grades 3-4) mucositis. RESULTS Sixty patients were randomized. Grade 2 + oral pain was higher with placebo (79% vs 45%; P = .0165), whereas grade 2 + body odor was greater with D-met (3% vs 41%; P = .0015). Mucositis was decreased with D-met by the physician (World Health Organization [WHO], P = .007; Radiation Therapy Oncology Group [RTOG], P = .009) and patient functional scales (RTOG, P = .0023). The primary end point of grades 3 to 4 mucositis on the composite scale demonstrated a decrease with D-met (48% vs 24%; P = .058), which was borderline in significance. A planned secondary analysis of a semiquantitative scoring system noted decreased oral ulceration (2.2 vs 1.5; P = .023) and erythema (1.6 vs 1.1; P = .048) with D-met. CONCLUSION Although not meeting the primary end point, results of multiple assessments suggest that D-met decreased mucositis.
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[11 C]Methionine emerges as a new biomarker for tracking active myeloma lesions.
Lapa, C, Schreder, M, Lückerath, K, Samnick, S, Rudelius, M, Buck, AK, Kortüm, KM, Einsele, H, Rosenwald, A, Knop, S
British journal of haematology. 2018;(5):701-703
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Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women.
Lamers, Y, Coats, B, Ralat, M, Quinlivan, EP, Stacpoole, PW, Gregory, JF
The Journal of nutrition. 2011;(5):835-42
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Abstract
Methionine is the precursor for S-adenosylmethionine (SAM), the major 1-carbon donor involved in >100 transmethylation reactions. Homocysteine produced from SAM must be metabolized either by remethylation for recycling of methionine or transsulfuration to form cystathionine and then cysteine. Pyridoxal 5'-phosphate (PLP) serves as a coenzyme in enzymes involved in transsulfuration as well as for primary acquisition of 1-carbon units used for remethylation and other phases of 1-carbon metabolism. Because the intake of vitamin B-6 is frequently low in humans and metabolic consequences of inadequacy may be amplified in the postprandial state, we aimed to determine the effects of marginal vitamin B-6 deficiency on the postprandial rates of remethylation, transmethylation, overall transsulfuration, and cystathionine synthesis. Healthy, young adults (4 male, 5 female; 20-35 y) received a primed, constant infusion of [1-(13)C]methionine, [methyl-(2)H(3)]methionine, and [5,5,5-(2)H(3)]leucine to quantify in vivo kinetics at normal vitamin B-6 status and after a 28-d dietary vitamin B-6 restriction. Vitamin B-6 restriction lowered the plasma PLP concentration from 49 ± 4 nmol/L (mean ± SEM) to 19 ± 2 nmol/L (P < 0.0001). Mean remethylation, transsulfuration, and transmethylation rates did not change in response to vitamin B-6 restriction; however, the responses to vitamin B-6 restriction varied greatly among individuals. The plasma cystathionine concentration increased from 142 ± 8 to 236 ± 9 nmol/L (P < 0.001), whereas the fractional cystathionine synthesis rate increased by a mean of 12% in 8 of 9 participants. Interrelationships among plasma concentrations of glycine and cystathionine and kinetic results suggest that individual variability occurs in normal postprandial 1-carbon metabolism and in the response to vitamin B-6 restriction.
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Variation in plasma cystathionine and its relation to changes in plasma concentrations of homocysteine and methionine in healthy subjects during a 24-h observation period.
Guttormsen, AB, Solheim, E, Refsum, H
The American journal of clinical nutrition. 2004;(1):76-9
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Abstract
BACKGROUND Plasma cystathionine measurement may be a useful complement to total homocysteine measurement in the assessment of B vitamin status. Information on the within-person variation in cystathionine is currently sparse. OBJECTIVE The goal was to study the daily variation in plasma cystathionine concentrations in healthy subjects. DESIGN Twelve subjects (aged 22-29 y) were followed for 24 h. During the observation period, the subjects received a breakfast (containing 15-18 g protein) at 0900 and a beef dinner (containing approximately 50 g protein) at 1500. Multiple blood samples for metabolite analyses were collected during the day, and a final sample was obtained the next morning. The results are expressed as medians and interquartile ranges. RESULTS All subjects had normal fasting cystathionine concentrations [0.120 (0.100-0.160) micro mol/L]. Cystathionine concentrations increased significantly after breakfast, reached a maximum after 4 h of 142.4% (100.0-170.3%) of the fasting concentration, and then declined to fasting concentrations before dinner. After dinner, plasma cystathionine started to increase within 0.5 h and reached a maximum after 6 h [281.3% (194.1-351.4%) of the concentration measured before dinner]. The changes in plasma methionine and total homocysteine concentrations during the day were less pronounced. CONCLUSION Food intake, even of foods with low protein content, causes an increase in plasma cystathionine concentrations that is more pronounced than the concomitant changes in total homocysteine and methionine. In studies including plasma cystathionine measurement, blood sampling in the fasting state should be considered.